The exact causes of multiple sclerosis are unknown. However, there is no doubt that there exists some conductive malfunction of the nerves, particularly the central nervous system. Neuropathologically, multiple lesions of the central nervous system (never the peripheral nervous system), are seen.
The general course of the disease among patients is characterized by exacerbation and remission of symptons. Such variations are almost indicative of the disease.
The disease is world-wide, but is most prevalent in temperate and cold climates. There appears to be no racial factor in the disease, but it is noted as more prevalent in females. Overt symptomology appears usually between the ages of 20 and 40 years. The disease affects an estimated half million Americans.
Etiological hypotheses for the disease, based on epidemiology, range from slow viruses, and immune system anomolies to heavy metal and esoteric metal poisonings. Some basis for each of these hypotheses have been found, but no incontrovertable proof has been forthcoming for any specific one or group.
Gross microscopic appearance of the brain and chord is often normal, but plaques of irregular grayish matter and grey areas may be seen in the white matter of the brain, brain stem and the ventricles, particularly the lateral and third ventricles. The size of these lesions from section to section of the spinal chord has been found in some cases to invade the entire cross-section of the chord. Also, it has been noted that there is a similarity between the demyelination of multiple sclerosis and the demyelination in pernicious anemia.
Microscopic examination of the lesions indicate demyelinazation of the nerve fibers. There is localized destruction of the myelin sheath, some damage to axis cylinders, proliferation of the glial cells and blood vessel changes. However, the ground structure appears preserved despite the fact that the microglial cells proliferate and phagocytize the debris, producing both fibrils and gross sclerotic changes.
The onset of symptoms may be acute with spasm paresthesias (prickling sensation), diplopia (double vision), amblyopia (dimmed vision), vertigo (dizziness) and hemiplegia (paralysis of one side of the body). Initially, the symptoms characteristically vary from day to day and shift from one extremity to another. The spinal form is often a spastic paraplagia, but frequently with intact cutaneous sensation. About 40% of the pateients have bladder dysfunction with urgency and incontinence.
Mental disturbances, primary or secondary, are found in about 95% of the cases--usually depression, but occasionally compensating euphoria and/or emotional liability.
During the choronic phase, Charcots' triad of scanning speech, intention tremor and nystagmus is often exhibited. Vertigo, ataxia and visual loss may precede the other symptoms much before a definitive diagnosis is possible.
Epidemiologically, it has been noted that about 40% of patients with retrobulbar neuritis (inflammation of the optic nerve at its junction with the eyeball) at ages 20 to 45 years will develop multiple sclerosis in 10 to 15 years. This is presently being intensively studied.
Two useful procedures are available diagnostically. The hot-bath test and individual eye examinations with Ishihara or pseudoisochromatic AO plates to detect alteration in color vision.
Alterations in color vision may occur even in patients who have never had a decrease or loss in visual acuity. The finding of such abnormalities points to an initial subclinical optic neuropathy caused by a lesion of the optic nerve. Such a finding supports the criterion of multiplicity of lesions for multiple sclerosis.
The hot-bath test is performed by immersing the patient in a hot bath (40.degree. C.). This test may cause the appearance of latent new symptoms and recurrence of previously experienced but undocumented transient symptoms and signs. Because of the intensity of the exacerbated symptoms, the patient must be under constant supervision during this test. Diplopia, loss or diminution of visual acuity, nystagmus, paresthesiae, changes in relfexes and Babinski signs may be demonstrated at this time. All these signs and symptoms regress once the patient has cooled so that the hot bath test may be considered as harmless.
These two tests are useful in that the single most important criterion in the diagnosis of multiple sclerosis is the demonstrated presence of more than one lesion of the central nervous system. The hot bath is useful in evoking the multiple latent effects of such lesions.
After such physical tests, chemical tests, for additional confirmation, are directed to such phenomena as the presence of oligoclonal bands in the gamma-globulin region upon electrophoresis of cerebrospinal fluid. This test is positive and identifying in 90% of patients with multiple sclerosis.
Recently greater insight has been afforded into the physiology of pain, its nature, its perception and its function under normal and diseased conditions by the discovery and study of endorphins and enkaphalins. The reactions of these compounds with, and at various sites along the nerves, the brain stem and the brain; have provided perspective as to nerve impulse conduction under normal and diseased conditions. Pain perception, pseudo-perception, exogenous and endogenous stimulation and their chemical effects, pinpoint the effects of demyelinization of the nerve fibers in the clinical course of the multiple sclerosis syndrome.
From these studies, it is now apparent that whether it is an electrolyte imbalance; demyelinization; anti-body reaction; alteration of receptor members, sites or nature; the impairment of nerve transmission to specific sites and muscles results in the muscular dysfunction seen in multiple sclerosis. To use an electrical analogy, the faulty switching, misdirection and imbalance of circuits causes the characteristic inability to use the proper and intended muscles due to spasm, pain or lack of properly directed stimulation as compared to normal nerve transmission.
In multiple sclerosis there is an obvious decrease in ascending and descending electrical transmission along nerves that are pathologically changed by demyelinization. It has been shown that demyelinized fibers do not transmit well so that nerve signals are delayed, misdirected or completely interrupted.
The electrical deficit thus noted has been the subject of my recent studies. I have previously found that degrees of relief of symptomatic pain are afforded by biphasic square wave nerve stimulation (Jr Med. Soc. N.J. Vol. 71 #5 pg. 365-367 May 74). Recently, it has been shown that such stimulation is related to the pain-perception mediation involving endorphins. The relationship of endorphin release in pain mediation by acupuncture, electro-acupuncture and transcutaneous nerve-stimulation (TNS) has recently been explored and confirmed by naloxone blocking and endorphin assay (B. Sjolund; L. Terenius; M. Eriksson; Acta physiol Scand 1977 #100 pp 382-384).
Recently, I have found that the electrical nerve conduction anomalies, painful as well as functional, as found in multiple sclerosis, can to some extent be reconstituted or mitigated by a course of TNS. In multiple sclerosis patients normal or near normal short term transmission and control is made possible by TNS treatment despite impairment due to demyelinization. Polarization and depolarization take place along the affected fibers. There appears to be a potentiation of the fibers despite the demyelinization areas of the nerve and spinal chord. This provides some short-term improvement in overt multiple sclerosis symptoms following the cessation of supply of electrical stimulation.
However, the remissions of specific symptoms, while immediate, are usually transient. In certain instances, the symptoms have returned within 24-48 hours, more extended relief is usually noted and in some cases the TNS treatment appears to have stimulated other remission mechanisms resulting in extended periods of relief.